The goals of this project are to define the effects of lithium on murine hematopoietic stem cells and its influence on stem cell self-renewal and differentiation. Hematopoietic stem cell changes will be studied first in normal mice given lithium chloride and will include a dose response of lithium on transplantable stem cells (CFU-S) and endogenous stem cells (E-CFU), in vitro granulocyte progenitor cells (CFU-C), splenic and marrow erythropoiesis using radioactive iron uptake, quantitation of marrow cellularity and blood leukocyte and platelet concentrations and hematocrit determinations. Using the best measures and optimum time and amount of lithium, the effects of lithium in hematopoietic regeneration will be examined following administration of cycle-specific and less cycle-specific cytotoxic drugs and following irradiation. The effects of lithium in experimental marrow hypoplasia will be studied in hypoplastic states induced by repetitive irradiation or busulfan administration. The ability of lithium to enhance granulopoietic recovery following single administration of cytotoxic drugs will be extended to evaluate changes in stem cell and granulopoietic recovery following repeated administration of cytotoxic drugs.